The role of quiescent and cycling stem cells in the development of skin cancer

Glind, G.C. van de (2018)

Doctoral Thesis

The incidence of skin carcinomas has been rising over the last decades. Ultraviolet (UV) radiation from the sun is the main exogenous risk factor. The principal premise underlying the present study is that stem cells are the primary targets of UV carcinogenesis. The aim of this study was to identify the main (stem) cell pool that drives this skin carcinogenesis. We studied cells in the interfollicular epidermis (IFE), quiescent stem cells and actively cycling Lgr5+ and Lgr6+ cells. Our data indicated that UV induced squamous cell carcinomas originate from the IFE. Furthermore, quiescent stem cells seem to play an important role in skin carcinogenesis. These cells accumulate DNA damage under chronic low level UV exposure. When we forced these DNA-damage retaining cells to proliferate, persistent (in situ) carcinomas developed. The actively cycling Lgr5+ and Lgr6+ cells did not seem to entail tumor-initiating stem cells in skin tumors induced by UV radiation or chemicals. We did not observe any tumors with substantial clonal expansion of Lgr5+ or Lgr6+ stem cells. Taken together, these results indicate that the continuously proliferating Lgr5+ and Lgr6+ stem cells are less vulnerable to cancerous transformation than quiescent stem cells.

• Damage retaining cells
• lgr5+ Stem cells
• lgr6+ Stem cells
• UV carcinogenesis
• Squamous cell carcinomas

• All authors: Glind, G.C. van de
• Supervisor: Willemze, R.
• Co-supervisor: Gruijl, F.R. de; Tensen, C.P.
• Committee: Vermeer, M.H.; GIbbs, S.; Garmyn, M.
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2018-04-18
• ISBN (print): 9789462998773
• Sponsorship: KWF